The fate
of a cell
describes what it will become in the course of normal development. The
fate of a particular cell can be discovered by labelling that cell and
observing what structures it becomes a part of. When the fate of all
cells
of an embryo has been discovered, we can build a fate map, which is a
diagram
of that organism at an early stage of development that indicates the
fate
of each cell or region at a later stage of development.

The developmental
potential,
or potency, of a cell describes the range of different cell types it
CAN
become. The zygote and its very early descendents are totipotent -
these
cells have the potential to develop into a complete organism.
Totipotency
is common in plants, but is uncommon in animals after the 2-4 cell
stage.
As development proceeds, the developmental potential of individual
cells
decreases until their fate is determined.

The determination
of different cell types (cell fates) involves progressive restrictions
in their developmental potentials. When a cell “chooses” a
particular fate,
it is said to be determined, although it still "looks" just like its
undetermined
neighbors. Determination implies a stable change - the fate of
determined
cells does not change.

Differentiation
follows
determination, as the cell elaborates a cell-specific developmental
program.
Differentiation results in the presence of cell types that have
clear-cut
identities, such as muscle cells, nerve cells, and skin cells.

Differentiation results from
differential gene expression:
The specific components of a given cell provides its special
characteristics.
These components are either synthesized by proteins, or are themselves
proteins. By expressing different subsets of genes, two cells contain
different
subsets of gene products (proteins).

How can we observe that cells from two tissues
express
different genes? Below are two blots: the Southern blot shows that
tissues
A and B both contain a particular gene. However, the Northern blots
shows
that only tissue A contains RNA transcribed from that particular gene.

Differential
gene
expression is not a result of differential loss of the genetic material,
DNA, except in the case of the immune system. That is, genetic
information
is not lost as cells become determined and begin to differentiate.

In fact, even the
nuclei of
adult cells contain ALL of the information needed for the construction
of an entire organism, if
provided with the proper cytoplasmic components. The cloning of Dolly
from
an adult cell is a major breakthrough, not only because of potential
biotechnological
applications, but because of the importance of this result for basic
science:
the result is the most convincing evidence for the theory of
differential
gene expression.

In order to clone Dolly, udder cells were
removed from
a Finn Dorset ewe and starved for one week to cause G0 arrest.
Nuclei
from arrested Finn Dorset udder cells were fused with enucleated eggs
from
a Scottish Blackface ewe, and then stimulated to re-enter the cell
cycle.
After a few rounds of cell division, the embryo was transplanted into a
surrogate Scottish Blackface mother. The sheep that was born was
genetically
identical to the Finn Dorset ewe, which was the source of the nucleus.

Transplantation of imaginal discs in insects
and the cloning
of whole plants from individual cells strengthens the conclusion that genetic
information is not lost as cells become determined and begin to
differentiate.

While differentiation results in specific cell
types,
morphogenesis
is the process whereby the shape (morph) of the embryo is generated
(genesis).
Morphogenesis in both plants & animals involves regulated patterns
of cell division and cell elongation that leads to changes in cell
shape.
Cell movement also plays a critical important role in animal
morphogenesis.

Mechanisms of
cellular determination

How do cells become different from their
parent cells?
How do two identical daughter cells become different from one another?
How might one daughter cell become a neuron, while the other daughter
cell
becomes a skin cell? In some cases, determination results from the asymmetric
segregation of cellular determinants. However, in most
cases,
determination is the result of inductive
signaling between cells.

Asymmetric
segregation of cellular determinantsis
based
on the asymmetric localization of cytoplasmic molecules (usually
proteins
or mRNAs) within a cell before it divides. During cell division, one
daughter
cell receives most or all of the localized molecules, while the other
daughter
cell receives less (or none) of these molecules. This results in two
different
daughter cells, which then take on different cell fates based on
differences
in gene expression. The localized cytoplasmic determinants are often
mRNAs
encoding transcription factors, or the transcription factors
themselves.
Unequal segregation of cellular determinants is observed during early
development
of the C. elegans (see
image below) and Drosophila embryos.

P-granule
segregation
during the early embryonic divisions of the nematode Caenorhabditis
elegans:

The image on the right shows an example
of asymmetric
segregation of cellular determinants in the early C.
elegans
embryo.
All of the cells in the embryo are visible on the left side of the
image,
while only the P granules are visible on the right side of the image.
The
P granules were fluorescently labelled - they are the green "dots".

a) A newly fertilized embryo with dispersed
P granules.

b) P granules are localized
to the posterior
end of the zygote.

c) After the first division, P
granules are present
only in the smaller, posterior cell.

d) Another unequal division gives
rise to a single
cell containing P granules.

e) When the larva hatches, P
granules are localized
to the primordial germ cells.

Although there are many examples where the
asymmetric segregation of cellular determinants leads to differences
between daughter cells, more frequently we find that cells become
different from one another as a result of inductive signals coming either
from other cells or from their external environment.

There
are many examples
in development where an inductive
signalfrom one group of cells
influences
the development of another group of cells.

There are three main ways in which
signals can be passed
between cells.

In the first mechanism, a
diffusible
signal is sent through the extracellular space,
and
is received by a cell-surface receptor, which further transmits the
signals
by way of second messengers.

In the second mechanism, cells directly
contact each other through transmembrane
proteins
located on their surfaces.

In the third mechanism, the cytoplasm of
two cells is
connected through gap junctions,allowing
the the signal to pass directly from one cell to another cell. In
plants,
direct connections between cells are called plasmodesmata.

Although one of the classic models for
signaling involves
diffusion, there is new evidence that inductive
signals
may in fact be actively transported within and between cells, and that
cellular projections may be involved in long distance communication
between
cells.

Pattern
formation

How do organs develop in their proper
positions? How do
cells "know" where they are within a developing organism? Pattern
formation
concerns the processes by which cells acquire positional information.

There are two general models for how patterns
form: use
of a morphogen
gradient, and sequential
induction.

The
morphogen
gradientmodel involves the production
and
release of a diffusible chemical signal called a morphogen.
Morphogen
release creates a concentration gradient, with high concentrations of
morphogen
close to the source, and low concentrations farther away from the
source.
Exposure to different threshold levels of morphogen leads to different
cell fates. In the example below, very high concentrations of the
morphogen
(above threshold 3) lead to the blue fate,
medium levels of morphogen (betweens thresholds 2 and 3) lead to the red
fate, and low levels of morphogen (between thresholds 1 and
2) lead to the purple fate. In
this
way, different amounts of one chemical signal can create a
complex
pattern.

What is an example of the use of a gradient
in pattern
formation??

The very first step in patterning the embryo
of the fruit
fly, Drosophila melanogaster, is a good example of pattern
formation
by a gradient. We'll talk more about Drosophila development
next
week. But for now, let's just use it as an example of this important
concept.

Bicoid is a transcription factor which turns
on different
genes in different levels - acting as a morphogen gradient. In this
way,
the four genes shown in part
A (tailless, empty
spiracles, hunchback,
and
kruppel)
are found in different locations within the Drosophila embryo, as a
result
of the amount of Bicoid protein at a particular location in the embryo.

After fertilization, bicoid mRNA from
the mother
fly begins to be translated into Bicoid protein in the Drosophila
zygote. The computer-generated image
B shows how the Bicoid protein diffuses through the egg forming a
gradient.
High concentrations of Bicoid protein are shown in white on the left
(anterior)
end of the zygote, and low concentrations are shown in blue on the
right
(posterior) end.

Image
C shows Bicoid protein in the nuclei of a Drosophila
embryo
after a number of rounds of mitosis. Notice that the nuclei in the
anterior
end (left) have more Bicoid protein than those in the posterior end
(right)
.

Image
D shows Kruppelprotein in orange
and Hunchback protein in green.
The region where the two proteins overlap is yellow.
The
colors come from fluorescent dyes attached to antibodies that bind
specifically
to these proteins.

The
sequential
inductionmodel involves the
production
and release of a series of chemical signals. Signal
1 leads to the blue
fate
and production of signal 2. Signal
2 is received by neighbor cells, and leads to the red
fate and production of signal 3.
Signal
3 is then received by neighbor cells, and leads to the purple
fate. In contrast to the morphogen gradient model, multiple
chemical signals are required to create the pattern.

What is an example of the use of sequential
induction
in pattern formation??

The development of the vulva (a ventral
opening used for
copulation and egg-laying) in the soil nematode,
Caenorhabditis elegans,
is a good example of pattern formation by sequential induction.

from Andreas
Eizinger and Ralf J. Sommer, Science 278:452-455 (1997)

This diagram of a larval nematode shows
the location of
cells which will become the vulva.

Vulval precursor cells P1.p through
P12.p are identical
to one another before the vulva develops. Vulval pattern formation
requires
the production of an initial signal (open arrow) by the anchor cell
(AC).
This signal is received by the vulval precursor cell called P6.p. The
signal
from AC changes P6.p in a way that alters signaling (by a second
signal)
between P5.p, P6.p and P7.p (filled arrows). As a result, vulval
precursor
cells P5.p and P7.p attain a high level of the protein LIN-12 (gray
shading),
but P6.p does not. That is, the combination of both signals
makes
P5.p and P7.p DIFFERENT FROM P6.p, and also different from their
neighbors
(shown in the top figure).